This document discusses the treatment of opioid use disorders. It begins by defining key opioid terminology and noting that while opioids are not directly toxic, they can cause lethal overdose. It then reviews the history of opioid use and regulation, including 19th century overprescription, the criminalization of addiction in the early 20th century, and the current opioid overdose epidemic in the US. The document outlines government responses like Risk Evaluation and Mitigation Strategies and CDC prescribing guidelines. It distinguishes physical dependence from addiction and notes medications used to treat opioid use disorders like antagonists, partial agonists, methadone, and buprenorphine.

1. Treatment of
Opioid Use Disorders
ChiefClinicalOfficer ClinicalProfessorofPsychiatry
GeorgetownUniversitySchoolof
Medicine
UniversityofMarylandSchoolof
Medicine
GeorgeKolodner, M.D.

2. Opioid Terminology
• Opiates: naturally occurring in opium poppy
(morphine, codeine)
• *Opioids: broader term includes naturally
occurring plus synthetics (heroin,
methadone, oxycodone)
• Narcotics: legal term, includes cocaine

3. Paradox: Relatively Harmless But Lethal
• Not tissue toxic
– Compare to alcoholand tobacco
– Infectiousdiseases linked to non-sterile needles
– Malnutrition linked to dietaryneglect
• Acute death by overdose
– Downregulationof receptorsduring periods of
abstinence lead to re-sensitizing of CNS
respiratorycentersin brain stem

4. Opioid Cautions and Reassurances
• 400 BC. Hippocrates: “Use sparingly”
• 1853. Hypodermic syringe
– “Decreaseaddiction by avoiding stomach”
• 1898. Bayer Heroin
– “Less addictive than morphine for coughs”
– Compare to BayerAspirin

5. 19th C. Opioid Medication Epidemic
• 1870s – 80s: Overuse of hypodermic
injection by physicians
• 1890’s – 1910s: Change to more balanced
prescribing patterns through education
and pressureby reform minded physicians
and pharmacists
– NEJM373:22,2095-7,2015.DavidCourtwright,Preventingand
TreatingNarcoticAddiction

6. Criminalization of Opioid Addiction
• 1915: Harrison Narcotic Act was intended
to keep narcotic transactions within
legitimate medical channels
– Actuallyimplemented by TreasuryDepartment
in a waythat interferedwith treatmentof
addiction
• The treatment of addiction is “outside the
realm of legitimate medical interest.”
– Webb etal vs. United States,1919
Legalto treatpain with opioids but not the
addiction which sometimesdeveloped

7. Opioid Related Overdose Deaths United States,
1999-2013

8. Death Rates by Age Group from Overdoses of
Heroin or Prescription Opioid Pain Relievers (OPR)
SOURCE: CDC. Increases in Heroin Overdose Deaths — 28 States, 2010 to 2012
MMWR. 2014, 63:849-854

9. Rates of Opioid Sales & OD Deaths
1999–2013
0
1
2
3
4
5
6
7
8
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Source:NationalVitalStatisticsSystem,DEA’sAutomationofReportsandConsolidatedOrdersSystem

10. Government Responses
• 2007: FDA given broader powers by
Congress to deal with “epidemic” of opioid
prescribing
– Risk Evaluationand MitigationStrategies
(“REMS”)
• 2015: Maryland Board of Physicians
mandate for one hour of CME per renewal
cycle
• 2016: Center for Disease Control CDC
Guidelines for Prescribing Opioids for
Chronic Pain

11. Risk Evaluation and Mitigation Strategies
(“REMS”)
• Refers to a variety of measures,beyond
traditional package labeling, that the FDA
can take to minimize the risks of a particular
medication
• Major focus has been on extended release,
long acting (ER/LA) opioids
– Developmentof new formulationsto reduce
diversion
– Educationof prescribing physicians

12. CDC Guidelines: Prescription of Opioid
Medications for Chronic Pain (January, 2016)
1. Non-pharmacologic and non-opioid
pharmacologic therapies are preferred
2. Beforestarting, discuss risks and benefits,
reasonablegoals for pain and functioning,
and have plan for discontinuation
3. Begin with immediate-releaseinstead of
extended-release/long-acting (ER/LA)
opioids
4. Periodically reevaluate and work to lower
dose or discontinue

13. CDC Guidelines: Prescription of Opioid
Medications for Chronic Pain (January, 2016)
5. Use urine testing before starting and
periodically thereafter
6. Use Prescription Drug Monitoring Program
(PDMP)
7. Avoid using opioids for patients taking
benzodiazepine medication
8. Screen for history of substance use
disorder

14. Confusion Between “Physical
Dependence” and “Addiction”
• To try reduce confusion, diagnostic
terminology was changed in DSM-5
from:
• “Opioid (etc.) Dependence/Abuse” to
• “Opioid (etc.) Use Disorder”
• “Abuse” = “Mild”
• “Dependence” = “Moderateor
Severe”

15. Physical Dependence
• Onset of withdrawal symptoms upon the
cessation of a substance
– Unmasks neuro-adaptations that have occurred
in response to use of substance
• Neurobiology
– Locus coeruleus (noradrenergic)
Irritability,increasedheartrateandBP,hyperalgesia
– Rewardcenters(dopaminergic)
Anhedonia,depression

16. Operational Diagnosis of Addiction
• Continued use of psychoactivesubstances
despite a pattern of adverse consequences
– Substance use is under poor control and
increasesin volume
– The substance occupies a centralplace in the
person’s life and leads to behavior that is out of
characterand violatesthe person’s usual values
• Diagnosis is based on the consequences of
using – not on the amount or frequency

17. 32
23
17 15
11 9 9
5 4
Percentageof Substance Users Who
Become Addicted,by Substance

18. Change in Substance Use by Kolmac
Patients
1989 2016
Cocaine 44% 9%
Opioids 6% 31%
Marijuana 6% 17%
Benzodiazepin
es
2% 8%

19. Treatment of Opioid Use Disorders
• Withdrawal management is needed more
frequently than with substances other than
tobacco
• “Abstinence-based” treatment has been
less successful than for other substances
• Controversyabout the balance between
therapy and medication
• Controversyabout the role of agonist and
antagonist medication

20. Agonists and Antagonists
• Full agonist: attachesto opioid receptorand fully
activatesit
– Opium,morphine,codeine,oxycodone(Oxycontin,
Percocet),hydrocodone(Vicodin),methadone
• Antagonist: attachesto opioid receptorand blocks
it instead ofactivatingit
– Naltrexone(Revia,Vivitrol)
• Partialagonist: attachesto opioid receptor,
partiallyactivatesand blocks it
– Buprenorphine(Suboxone)

21. Antagonists
• Naloxone(“Narcan”)
– Reversesopioid overdose
– Immediateeffectwith short duration
– Injectableor nasal
• Naltrexone
– Used for relapseprevention
– Used long term (months to years)
– Formulations
• Oral(“Revia”)
• Depotinjectionlastsfor1month(“Vivitrol”)

22. Opioids For Addiction Treatment:
A Change of Approach
• Methadone
– 1937.DevelopedinGermanyforpain
– 1971.ApprovedinUSAfordetoxificationand
maintenanceofopioidaddicts
– Highlyrestricteduse–regulatedprograms(OTP)
– Nowtakenbyabout250,000patientsinUS
• Buprenorphine
– 1978.Parenteralformulationforpain
– 2000–2003.Approvalforaddictiontreatment
– Availableforofficebaseduseby“waivered”prescribers
• InitiallyonlyphysiciansbutnowalsoNPsandPAs
– Nowtakenbyabout1,000,000patientsinUS

23. Buprenorphine FDA Approval
DEA Schedule III
• For pain
– Parenteral(Buprenex)
– Transdermal(Butrans)
• For addiction (buprenorphine waiver and
DEA “X” number required)
– Sublingual (Suboxone, Zubsolv, generic)
– Buccal(Bunavail)

24. Advantages of Buprenorphine
1. Safer from overdose
– Ceilingon respiratorydepression
• Benzodiazepinesraiseceiling
2. Rarely causes euphoria unless taken IV
– Partialmu agonist
3. Blocks most other opioids
– High affinityfor receptorsites
4. Can eliminate all withdrawal symptoms
including craving

25. Experience with Buprenorphine at Kolmac
• Compared to naltrexone
– Doubling of completionratein rehabilitation
phase
• Noreductionincompletionrateofnon-opioid
patients
– Substantial participationin continuing care
phase
– Reduction in overdose deaths
• Improves the patient’s ability to do the
psychological work of recovery
– Ancillarynot curative

26. Buprenorphine vs. Methadone
in Pregnancy
• Same incidence of neonatal abstinence
syndrome (NAS)
• Less severeNAS with buprenorphine
– 89 % less medication
– 43% fewerhospital days
• More discontinuation of buprenorphine
than methadone because of dissatisfaction
with medication
• Methadone still the official standard of care

27. Resistance to MAT in Recovery Community
• NarcoticsAnonymous
• 12-Step based residential rehabilitation
programs
• Hazelden/Betty Ford Breaking ranks
• Forcing redefinition of “recovery”
– WilliamWhite: www.williamwhitepapers.com

28. Modern Addiction Recovery
kolmac.com/category/articles
Send requests for addiction topics to:
gkolodner@kolmac.com
Thank You!